The metabolic and functional heterogeneity of human platelets will be further studied with respect to human platelet senescence. Large- heavy platelets have been shown to be probable "young" platelets which progress with age to small-light "older" platelets. A search will be made for the rate-limiting processes responsible for platelet senescence. Regulator enzymes of specific energy pathways will be examined. The contributions of the Embden-Meyerhof, Krebs cycle and Hexosephosphate shunt pathways will also be examined. The use of the large platelet (on peripheral smear) as an index of thrombopoiesis, will be pursued, with respect to its correlation with megakaryocyte number, platelet volume and platelet survival. Information obtained from "young and "old" platelets will be employed to develop a more sensitive test for the postulated enzyme, 'thrombopoietin'. The biochemistry of platelet adhesion will be examined following the development of an adequate technique for measuring platelet adhesion to collagen. If such a technique can be established it would be of value in selecting pharmacologic agents which might control platelet adhesiveness. These agents might conceivably be of value in the treatment and prophylaxis of atherosclerosis in general and coronary artery disease in particular.